This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The project will develop and test tools based on advanced diffusion MRI methods of diffusion spectral imaging (DSI) to map structural changes in white matter architecture and connectivity in early Alzheimer's dementia. Using diffusion tensor MRI, CIND Investigator Dr. Y Zhang et. al. [Zhang 2007] have recently demonstrated that structural changes with the fibers of the cingulum bundle of the medial temporal lobe have potential as a specific early marker of Alzheimer's disease. The Aims of this section are: 1. Translate and optimize DSI technology for use in human subjects with cognitive impairment. 2. Devise robust procedures of data reduction and analysis to map the cingulum bundle and quantify it structural integrity. 3. Evaluate the capacity of DSI to differentiate normal from abnormal structure of the cingulum bundle and other major fiber tracts of the temporal lobe in the Alzheimer's population.